A. Technical Field
The technical field relates to using fluorescence or fluorescence lifetime decay of oxygen sensors to measure multiple parameters simultaneously such as pH, blood gases, electrolytes, immunoassay and hematology in a handheld miniaturized format using inexpensive electronics for illumination, detection, lancet actuation and data communication. Alternatively, electrochemical tests suitable for point of care testing can be employed.
B. Related Art
POC (point of care) testing is attractive because it rapidly delivers results to the medical practitioner and enables faster consultation with the patient enabling the practitioner to commence treatment sooner, perhaps leading towards improved patient outcomes. Relevant art includes the use of screening and monitoring diagnostics for early intervention, such as cardiac markers for early detection of angina, coronary artery occlusion and ruling out chest pain (triage). Examples of POC tests include blood chemistry such as glucose, lactate, electrolytes, as well as hematology, immuno-diagnostics, drugs of abuse, serum cholesterol, fecal occult blood test (“FOBT”), pregnancy, and ovulation. Examples of electrochemical Point of Care devices, which are hand, held are given by the i-STAT where electrochemical tests are carried out on a few drops of blood. Based on Microfabricated thin film electrodes, common tests include creatinine, or glucose on single cartridges, or combined tests such as sodium, potassium, hematocrit and hemoglobin on a single cartridge. Tests are combined on cartridges depending on the application e.g. blood gas panel etc. One disadvantage to this deployment of tests on panel specific cartridges is that in some cases several cartridges may be used to obtain complete POC information from the patient.
Current POC devices such as the i-STAT do not provide an integrated solution for patient self-testing for sample acquisition, testing, analysis and connectivity to remote centralized healthcare. Accordingly it is the object of this invention to provide a portable, highly integrated, multi-parameter measurement instrument where sampling is integrated with measurement processes from 1 μL of blood or less. Integration will allow the broad deployment of tests for a single sample acquisition step. This fully integrated blood sampling and measurement technology platform has been established for glucose spot monitoring, (WO 02/1000254 Lancet launching device integrated on to a blood sampling cartridge) in a multi-test format (100+ tests) employing an electronic blood-sampling device (WO 02/100460 Electric lancet actuator, WO 02/100251 Self optimizing lancing device) embedded within a glucose measurement instrument and a data management system (WO 02/101359 Integrated blood sampling and analysis system with multi use sampling module). Optical measurement of analytes provides the potential to monitor important clinical analytes for Point of Care applications. Fluorescent amplitude or lifetime decay optical measurements of glucose can be made with low-cost, low-power consumption components that are compatible with handheld instrumentation. These components include LED's, plastic optical elements, and CMOS or photodiode light detectors. The opportunity exists to carry out multiple measurements on the same sample to obtain more precise results or to analyze for components other than glucose (U.S. Pat. No. 6,379,969 Optical sensor for sensing multiple analytes)
These POC still use a body fluid sample. Obtaining such a sample using conventional lancing device can be painful. Early methods of lancing included piercing or slicing the skin with a needle or razor. Current methods utilize lancing devices that contain a multitude of spring, cam and mass actuators to drive the lancet. These include cantilever springs, diaphragms, coil springs, as well as gravity plumbs used to drive the lancet. The device may be held against the skin and mechanically triggered to ballistically launch the lancet. Unfortunately, the pain associated with each lancing event using known technology discourages patients from testing. In addition to vibratory stimulation of the skin as the driver impacts the end of a launcher stop, known spring based devices have the possibility of firing lancets that harmonically oscillate against the patient tissue, causing multiple strikes due to recoil. This recoil and multiple strikes of the lancet is one major impediment to patient compliance with a structured glucose monitoring regime.
Another impediment to uncomfortable patient experience of giving a blood sample is the lack of spontaneous blood flow generated by known lancing technology. In addition to the pain as discussed above, a patient may need more than one lancing event to obtain a blood sample since spontaneous blood generation is unreliable using known lancing technology. Thus the pain is multiplied by the number of attempts required by a patient to successfully generate spontaneous blood flow. Different skin thickness may yield different results in terms of pain perception, blood yield and success rate of obtaining blood between different users of the lancing device. Known devices poorly account for these skin thickness variations.
Measurement of glucose concentration is commonly based on the use of an enzyme such as glucose oxidase or glucose dehydrogenase. In such sensing schemes, glucose (substrate) is turned over by an enzyme layer resulting in change in the concentration of another species such as oxygen or hydrogen ion. The change in concentration of these species can be converted into some charge based or optical change at a transducer interface (sensing region). Alternatively, if the enzyme is electrically coupled to an inert electrode, such a reaction results in a change in electron flow at constant applied potential. Both types of transduction mechanisms are widely used in glucose sensing. In the former type of transduction scheme, the reaction zone can be decoupled from the sensing region. Thus, the reaction of the enzyme with the substrate can be brought about in one region and the concentration measurement can be done in another region. In the latter scheme, the enzymatic reaction has to occur in close proximity to the sensing region (electrode surface) for electrical coupling. Some devices may also include analyte detecting member for analyzing sample fluid. Unfortunately, the storage ability of these devices are limited due to the need for some of these elements to be stored in inert environments.
The current sensing technologies do not attempt the separate the reaction zone from the sensing region. One disadvantage of this approach is that the enzyme layer has to be placed in close proximity to the sensing element. This results in considerable difficulty in manufacturing and/or stabilizing the chemistries associated with enzymatic reaction and the transduction scheme. For example in the optical transduction schemes, an oxygen sensing layer such as a silicone rubber film doped with a flurophore, such as Ru Tris Diphenyl Phenanthroline, is coupled to the enzymatic layer containing glucose oxidase. The chemicals used in making these layers interfere with proper functioning of each other. There is often considerable reduction in the enzyme activity. The resultant sensors have limited dynamic range or limited shelf life or both.